Michigan Tech biochemist Tarun Dam with a solution containing lectin, used to study
how an important class of biomolecules react in the body. Sarah Bird photo

There’s a certain type of biomolecule built like a nano-Christmas tree. Called a glycoconjugate,
its many branches are bedecked with sugary ornaments.

It’s those ornaments that get all the glory. That’s because, according to conventional
wisdom, the glycoconjugate’s lowly “tree” basically holds the sugars in place as they
do the important work of reacting with other molecules.

Now a biochemist at Michigan Technological University has discovered that the tree
itself—called the scaffold—is a good deal more than a simple prop.

“We had always thought that all the biological function resides in the sugar,” said
Tarun Dam, principal investigator of the Mechanistic Glycobiology Lab at Michigan
Tech. “People didn’t appreciate that the scaffolds were active.”

The discovery opens up new avenues for research, in particular the development of
more and better pharmaceuticals. Glycoconjugates are found naturally in the body,
but they are also an important class of drugs that includes anything from cancer treatments
to vaccines.

To determine if the scaffold had a role to play in biological reactions, Dam and his
team built and tested two types of glycoconjugate molecules. They had the same sugars
and virtually identical shapes but were comprised of different scaffolds, one made
of protein, the other a synthetic. The scientists then tested how the different glycoconjugates
reacted with biomolecules called lectins. Lectins play an important role in numerous
biological processes and are a target for many glycoconjugate drugs.

If the scaffolds had been inert, the reactions would have been identical. However,
the sugars on the protein scaffold reacted with the lectins differently.

“If the scaffolds are different, they can cause my drug to work one way and your drug
to work another way, even though they have similar epitopes [sugars],” Dam said. “Tweaking
the scaffold can change the drug’s function.”

An article on their study, “Significant Other Half of a Glycoconjugate: Contributions of Scaffolds to Lectin-Glycoconjugate
Interactions,” was published in the July 15 edition of Biochemistry. In addition to Dam, the coauthors
are Michigan Tech chemistry graduate students Melanie Talaga, Ni Fan, Ashli Fueri
and Rob Brown; Yoann Chabre and René Roy of the Université du Québec a Montréal; and
Purnima Bandyopadhyay, a research assistant professor of biological sciences at Michigan
Tech. Dam is an assistant professor of chemistry at Michigan Tech. The study was supported
by Michigan Tech and the Natural Science and Engineering Research Council of Canada.

Michigan Technological University is a public research university, home to more than
7,000 students from 54 countries. Founded in 1885, the University offers more than
120 undergraduate and graduate degree programs in science and technology, engineering,
forestry, business and economics, health professions, humanities, mathematics, and
social sciences. Our campus in Michigan’s Upper Peninsula overlooks the Keweenaw Waterway
and is just a few miles from Lake Superior.